THE INSERTION ALLELE OF THE ACE GENE I D POLYMORPHISM - A CANDIDATE GENE FOR INSULIN-RESISTANCE/

Background The insertion/deletion (ID) polymorphism of the angiotensin -converting enzyme (ACE) gene has been associated with increased coron ary heart disease (CHD), although the mechanism of this association is not apparent. We tested the hypothesis that the deletion allele of th e ACE gene is associated with insulin resistance. Methods and Results We related ACE genotype to components of the insulin-resistance syndro me in 103 non-insulin-dependent diabetic (NIDDM) and 533 nondiabetic w hite subjects. NIDDM subjects with the DD genotype had significantly l ower levels of specific insulin (DD 38.6, ID 57.1, and II 87.4 pmol L( -1) by ANOVA, P=.011). Non-insulin-treated subjects with the DD genoty pe had increased insulin sensitivity by HOMA % (DD 56.4%, II 29.4%, P= .027) and lower levels of des 31,32 proinsulin (DD 3.3, II 7.6 pmol . L(-1), P=.012) compared with II subjects. There were no differences in prevalence of CHD or levels of blood pressure, serum lipids, or plasm inogen activator inhibitor-1 (PAI-1) activity between the three ACE ge notypes. In nondiabetic subjects there were no differences in insulin sensitivity, levels of insulin-like molecules, blood pressure, PAI-1, serum lipids, or CHD prevalence between the three ACE genotypes. Concl usions We conclude that increased cardiovascular risk of the DD genoty pe is not mediated through insulin resistance or abnormalities in fibr inolysis. Conversely, we report an increased sensitivity in NIDDM subj ects with the ACE DD genotype.